Highly Efficient Uptake of a Rifamycin Derivative via the FhuA-TonB-dependent Uptake Route in Escherichia coli

SUMMARY: Rifamycin CGP 4832 is a semisynthetic rifamycin derivative. It is at least 200 times more active than rifampicin against Escherichia coli and related bacteria. This increased activity is shown here to be due to the efficient uptake of CGP 4832 across the E. coli outer membrane via the ferrichrome transport system comprising the outer membrane FhuA (TonA) protein, the ferrichrome receptor, and the inner membrane TonB protein. CGP 4832 competed with ferrichrome and other iron siderophore complexes, and with bacteriophage T5 and colicin M for binding sites on the FhuA protein. Mutations in fhuA or tonB genes reduce CGP 4832 sensitivity to a level comparable to that to rifampicin. There is no evidence that CGP 4832 or rifampicin utilize the inner membrane ferrichrome transport system to gain entry into the cytoplasm.